Liver Fibrosis, Hepatitis C Virus
Conditions
Keywords
Staging of liver fibrosis prior to clinical trials for treatment of Hepatitis C Virus
Brief summary
This study will assess the repeatability of Magnetic Resonance Elastography (MRE) in both healthy volunteers and Hepatitis C Virus (HCV)-infected patients with fibrosis and lay the groundwork for the validation of MRE as an alternative to liver biopsy.
Interventions
PROCEDUREMRE
Part 1: Participants will have a screening visit, followed \ 1 month later by two imaging visits over \ 14 days. Each imaging visit will consist of two liver MRE scans. Part 2: Participants will have a screening visit, followed \ 1 month later by one imaging visit. The imaging visit will consist of two liver MRE scans.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Male or female and at least 18 years of age * Generally good health * Willing to fast for 8 hours prior to each study visit Hepatitis C Virus (HCV) Inclusion Criteria: * Positive serology for HCV and detectable HCV ribonucleic acid (RNA) in blood within 12 weeks of screening; For Part I, known fibrosis stage of at least =F2 (METAVIR) or =F3 (Ishak) from biopsy performed within 3 months of screening; For Part 2, known fibrosis stage of F1-F4 (METAVIR) or F1-F6 (Ishak) * Never been treated for HCV Healthy Participant Inclusion Criteria: * Documented absence of hepatitis B virus, HCV, acute hepatitis A virus, and human immunodeficiency virus (HIV) within 12 weeks of screening
Exclusion criteria
* History of stroke, seizures, or neurological disorders * Consumption of excessive amounts of alcohol * Use of products containing nicotine * Unable to hold a breath for 20 seconds * Claustrophobia * Use of illicit drugs or history of drug or alcohol abuse HCV-Positive
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Repeated Maximum Liver Elastic Stiffness (Kilopascal [kPa]) Measurements | 14 days | Reader evaluated 4 sections of the liver at 4 different time points and the end result was a single region of interest (ROI) that could be measured in the registered elastograms at each of the time points. Stiffness measures obtained using the Individual ROI (average of the 4 individual ROI's selected by the reader, one for each slice of liver) and Common ROI (intersection (or area of common overlap) of the 4 individual ROI's) analysis methods were compared. The mean was the overall mean of the data and the standard deviation was the within participant standard deviation. |
| Repeated Mean Liver Elastic Stiffness (kPa) Measurements | 14 days | Reader evaluated 4 sections of the liver at 4 different time points and the end result was a single ROI that could be measured in the registered elastograms at each of the time points. Stiffness measures obtained using the Individual ROI (average of the 4 individual ROI's selected by the reader, one for each slice of liver) and Common ROI (intersection (or area of common overlap) of the 4 individual ROI's) analysis methods were compared. The mean was the overall mean of the data and the standard deviation was the within participant standard deviation. |
| Percent Difference in Mean Liver Stiffness Between Hepatitis C Virus (HCV)- Positive Participants With Liver Fibrosis and Healthy Participants | 14 days | Reader evaluated 4 sections of the liver at 4 different time points and the end result was a single region of interest (ROI) that could be measured in the registered elastograms at each of the time points. Stiffness measures obtained using the Individual ROI (average of the 4 individual ROI's selected by the reader, one for each slice of liver) and Common ROI (intersection (or area of common overlap) of the 4 individual ROI's) analysis methods were compared. |
| Percent Difference in Maximum Liver Stiffness Between HCV- Positive Participants With Liver Fibrosis and Healthy Participants | 14 days | Reader evaluated 4 sections of the liver at 4 different time points and the end result was a single region of interest (ROI) that could be measured in the registered elastograms at each of the time points. Stiffness measures obtained using the Individual ROI (average of the 4 individual ROI's selected by the reader, one for each slice of liver) and Common ROI (intersection (or area of common overlap) of the 4 individual ROI's) analysis methods were compared. |
Participant flow
Pre-assignment details
Part 2 of the study was not conducted; however, in Part 2 of the study, participants would have had a screening visit, followed \ 1 month later by one imaging visit. The imaging visit would have consisted of two liver Magnetic Resonance Elastography (MRE) scans.
Participants by arm
| Arm | Count |
|---|---|
| Magnetic Resonance Elastography (MRE) In Part 1 of the study, participants had a screening visit, followed \
1 month later by two imaging visits over \
14 days. Each imaging visit consisted of two liver MRE scans. | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Claustrophobia during MRI | 1 |
Baseline characteristics
| Characteristic | Magnetic Resonance Elastography (MRE) |
|---|---|
| Age, Continuous | 45.5 years STANDARD_DEVIATION 12.9 |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Percent Difference in Maximum Liver Stiffness Between HCV- Positive Participants With Liver Fibrosis and Healthy Participants
Reader evaluated 4 sections of the liver at 4 different time points and the end result was a single region of interest (ROI) that could be measured in the registered elastograms at each of the time points. Stiffness measures obtained using the Individual ROI (average of the 4 individual ROI's selected by the reader, one for each slice of liver) and Common ROI (intersection (or area of common overlap) of the 4 individual ROI's) analysis methods were compared.
Time frame: 14 days
Population: Participants analyzed were Completers.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reader 1 | Percent Difference in Maximum Liver Stiffness Between HCV- Positive Participants With Liver Fibrosis and Healthy Participants | MRE Common ROI | 117.21 percent treatment difference |
| Reader 1 | Percent Difference in Maximum Liver Stiffness Between HCV- Positive Participants With Liver Fibrosis and Healthy Participants | MRE Individual ROI | 105.35 percent treatment difference |
| Reader 2 | Percent Difference in Maximum Liver Stiffness Between HCV- Positive Participants With Liver Fibrosis and Healthy Participants | MRE Common ROI | 91.24 percent treatment difference |
| Reader 2 | Percent Difference in Maximum Liver Stiffness Between HCV- Positive Participants With Liver Fibrosis and Healthy Participants | MRE Individual ROI | 90.77 percent treatment difference |
Primary
Percent Difference in Mean Liver Stiffness Between Hepatitis C Virus (HCV)- Positive Participants With Liver Fibrosis and Healthy Participants
Reader evaluated 4 sections of the liver at 4 different time points and the end result was a single region of interest (ROI) that could be measured in the registered elastograms at each of the time points. Stiffness measures obtained using the Individual ROI (average of the 4 individual ROI's selected by the reader, one for each slice of liver) and Common ROI (intersection (or area of common overlap) of the 4 individual ROI's) analysis methods were compared.
Time frame: 14 days
Population: Participants analyzed were Completers.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reader 1 | Percent Difference in Mean Liver Stiffness Between Hepatitis C Virus (HCV)- Positive Participants With Liver Fibrosis and Healthy Participants | MRE Common ROI | 94.41 percent treatment difference |
| Reader 1 | Percent Difference in Mean Liver Stiffness Between Hepatitis C Virus (HCV)- Positive Participants With Liver Fibrosis and Healthy Participants | MRE Individual ROI | 97.02 percent treatment difference |
| Reader 2 | Percent Difference in Mean Liver Stiffness Between Hepatitis C Virus (HCV)- Positive Participants With Liver Fibrosis and Healthy Participants | MRE Common ROI | 94.66 percent treatment difference |
| Reader 2 | Percent Difference in Mean Liver Stiffness Between Hepatitis C Virus (HCV)- Positive Participants With Liver Fibrosis and Healthy Participants | MRE Individual ROI | 99.31 percent treatment difference |
Primary
Repeated Maximum Liver Elastic Stiffness (Kilopascal [kPa]) Measurements
Reader evaluated 4 sections of the liver at 4 different time points and the end result was a single region of interest (ROI) that could be measured in the registered elastograms at each of the time points. Stiffness measures obtained using the Individual ROI (average of the 4 individual ROI's selected by the reader, one for each slice of liver) and Common ROI (intersection (or area of common overlap) of the 4 individual ROI's) analysis methods were compared. The mean was the overall mean of the data and the standard deviation was the within participant standard deviation.
Time frame: 14 days
Population: Participants analyzed were Completers.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reader 1 | Repeated Maximum Liver Elastic Stiffness (Kilopascal [kPa]) Measurements | MRE Common ROI | 4.54 kPa | Standard Deviation 0.48 |
| Reader 1 | Repeated Maximum Liver Elastic Stiffness (Kilopascal [kPa]) Measurements | MRE Individual ROI | 5.10 kPa | Standard Deviation 0.44 |
| Reader 2 | Repeated Maximum Liver Elastic Stiffness (Kilopascal [kPa]) Measurements | MRE Common ROI | 4.64 kPa | Standard Deviation 0.5 |
| Reader 2 | Repeated Maximum Liver Elastic Stiffness (Kilopascal [kPa]) Measurements | MRE Individual ROI | 5.14 kPa | Standard Deviation 0.41 |
Comparison: ICC for measures of liver stiffness obtained by MRE (i.e., average over all 4 slices of the maximum stiffness for each slice) with respect to repeatability (precision) of multiple MRE assessments. This pertains to the Common ROI.90% CI: [0.81, 0.99]
Comparison: ICC for measures of liver stiffness obtained by MRE (i.e., average over all 4 slices of the maximum stiffness for each slice) with respect to repeatability (precision) of multiple MRE assessments. This pertains to the Common ROI.90% CI: [0.71, 0.98]
Comparison: ICC for measures of liver stiffness obtained by MRE (i.e., average over all 4 slices of the maximum stiffness for each slice) with respect to repeatability (precision) of multiple MRE assessments. This pertains to the Individual ROI.90% CI: [0.78, 0.98]
Comparison: ICC for measures of liver stiffness obtained by MRE (i.e., average over all 4 slices of the maximum stiffness for each slice) with respect to repeatability (precision) of multiple MRE assessments. This pertains to the Individual ROI.90% CI: [0.75, 0.98]
Primary
Repeated Mean Liver Elastic Stiffness (kPa) Measurements
Reader evaluated 4 sections of the liver at 4 different time points and the end result was a single ROI that could be measured in the registered elastograms at each of the time points. Stiffness measures obtained using the Individual ROI (average of the 4 individual ROI's selected by the reader, one for each slice of liver) and Common ROI (intersection (or area of common overlap) of the 4 individual ROI's) analysis methods were compared. The mean was the overall mean of the data and the standard deviation was the within participant standard deviation.
Time frame: 14 days
Population: Participants analyzed were Completers.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reader 1 | Repeated Mean Liver Elastic Stiffness (kPa) Measurements | MRE Common ROI | 3.12 kPa | Standard Deviation 0.26 |
| Reader 1 | Repeated Mean Liver Elastic Stiffness (kPa) Measurements | MRE Individual ROI | 3.08 kPa | Standard Deviation 0.19 |
| Reader 2 | Repeated Mean Liver Elastic Stiffness (kPa) Measurements | MRE Common ROI | 3.14 kPa | Standard Deviation 0.31 |
| Reader 2 | Repeated Mean Liver Elastic Stiffness (kPa) Measurements | MRE Individual ROI | 3.15 kPa | Standard Deviation 0.2 |
Comparison: ICC for measures of liver stiffness obtained by MRE (i.e., average over all 4 slices of the maximum stiffness for each slice) with respect to repeatability (precision) of multiple MRE assessments. This pertains to the Common ROI.90% CI: [0.8, 0.99]
Comparison: ICC for measures of liver stiffness obtained by MRE (i.e., average over all 4 slices of the maximum stiffness for each slice) with respect to repeatability (precision) of multiple MRE assessments. This pertains to the Common ROI.90% CI: [0.78, 0.99]
Comparison: ICC for measures of liver stiffness obtained by MRE (i.e., average over all 4 slices of the maximum stiffness for each slice) with respect to repeatability (precision) of multiple MRE assessments. This pertains to the Individual ROI.90% CI: [0.87, 1]
Comparison: ICC for measures of liver stiffness obtained by MRE (i.e., average over all 4 slices of the maximum stiffness for each slice) with respect to repeatability (precision) of multiple MRE assessments. This pertains to the Individual ROI.90% CI: [0.88, 1]